# Antibody landscapes of arboviral exposure across China revealed by high-throughput seroprofiling from a peptide epitope library

## TL;DR

This study maps antibody responses to arboviruses across China, revealing regional and demographic patterns that could improve surveillance and prevention strategies.

## Contribution

The study introduces ArboScan, a high-throughput seroprofiling platform using a peptide epitope library to quantify population-level arboviral immunity.

## Key findings

- Northern regions showed higher antibody reactivity to bluetongue virus, while southern regions showed higher reactivity to mosquito-borne arboviruses.
- Females exhibited higher antibody reactivity than males for certain arboviral families.
- Stable antibody levels across age groups suggest immunity is not strongly influenced by age.

## Abstract

Arboviral infections impose significant public health challenges globally, yet routine surveillance typically captures only symptomatic infections, underestimating the true extent of exposure. Insights into how regional and demographic factors influence population immunity are essential for targeted surveillance and prevention, but such multidimensional insights remain limited. This study aimed to quantify population-level arboviral sero exposure and delineate the effects of regional and demographic factors on immunity to inform targeted surveillance and prevention.

We utilized a programmable phage display platform, ArboScan, which evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We profiled baseline antibody reactivity in serum samples from 400 healthy individuals, collected before the dengue outbreaks reported in Hainan in 2019. Antibody reactivity was quantified as normalized fold-change (FC) values relative to negative controls, and analyzed by region, sex, and age. Normality was assessed using the Shapiro-Wilk test. Two-group comparisons were conducted using independent two-sample t tests for normally distributed data or Mann-Whitney U tests otherwise; comparisons among > 2 groups were performed using One-way Analysis of Variance for normally distributed data.

Regional ranking by mean product fold change (MPFC) showed northern enrichment for bluetongue virus (MPFC = 3.56), whereas southern cohorts were enriched for mosquito-borne arboviruses-dengue virus (MPFC = 3.54), Alagoas vesiculovirus (MPFC = 3.50), and Venezuelan equine encephalitis virus (MPFC = 3.39). Females exhibited higher FC than males for selected arboviral families (P < 0.001). By family-level analysis, Flaviviridae, Togaviridae, and Phenuiviridae showed no age-stratified differences (P > 0.05). High fold-change values were detected for non-arboviral viruses such as human cytomegaloviruses and human adenoviruses across all regions.

Our findings reveal distinct regional and demographic patterns of arboviral antibody reactivity in China, reflecting differing histories of exposure and potentially informing region-specific surveillance strategies. The stable antibody levels across age groups, together with higher fold-change values in females, underscore the influence of biological and social factors on arboviral immunity. The ArboScan platform, and programmable peptide display platforms in general, offer a scalable approach to characterize population-level immunity and could enhance early detection and public health preparedness in arbovirus-endemic areas.